The broad objective of this proposal and our research efforts is to fully understand the cellular and molecular immunological events involved in induction of murine IgA responses. A common mucosal immune defense systems exists in which sensitization of lymphoreticular cells to ingested antigens occurs in gut-associated lymphoreticular tissue (GALT), e.g., Peyer's patches (PP), followed by homing of sensitized cells to distant mucosal regions for IgA expression. Homing of regulatory cells from PP to peripheral tissue may mediate systemic unresponsiveness to ingested antigens. We will determine the roles for each PP lymphoreticular cell type involved in the induction of IgA, and regulation of other isotype, responses. Adherent cells (macrophages, dendritic cells and follicular dendritic cell subtypes) will be purified from murine PP and their accessory cell functions established. Studies concerning regulation of IgA and other isotype responses by effector T cells will involve in vitro analysis of T helper (Th) and T suppressor (Ts) cell activities for polyclonal immunoglobulin synthesis and antigen-specific immune responses. The use of PP Th and Ts cell clones will facilitate understanding of T cell regulation in GALT. Mediators released by PP T cells capable of supporting IgA immune responses will be emphasized in our studies. We will determine the precise homing patterns of purified PP lymphoreticular cell subpopulations to tissues where isotype regulation and expression occur. These studies will provide the necessary framework for further studies with biologically relevant immunogens (e.g., vaccines, allergens, etc.) for induction of protective immunity in human external secretions.